Transfusion Medicine

NON-TRANSFUSION THERAPIES FOR ACUTE BLEEDING

DESMOPRESSIN

Desmopressin (DDAVP) is a synthetic analog of antidiuretic hormone that raises the levels of both factor VIII and von Willebrand protein severalfold.⁶⁶ Desmopressin is effective in supporting hemostasis in patients with a wide variety of congenital and acquired bleeding disorders. However, desmopressin does not reduce blood loss before routine surgery in a healthy patient and should not be used for this purpose.⁶⁷

TRANEXAMIC ACID

Tranexamic acid is an antifibrinolytic agent that blocks the binding of plasmin to fibrin.⁶⁸ This agent was first shown to be useful in disorders that involve excessive fibrinolysis^69–73 or as adjunctive therapy for oral or dental procedures in patients with a bleeding diathesis. In patients with severe thrombocytopenia, the use of antifibrinolytic agents may reduce bleeding. Increasing data shows that tranexamic acid can prevent blood loss in a variety of surgeries including heart bypass, liver transplantation, and orthopedic surgery.⁷⁴ Patients across these settings have decreased blood loss and need for transfusion with no increased risk of thrombosis. The CRASH-2 study showed that the use of tranexamic acid significantly reduced mortality in trauma patients.⁷⁵ The WOMEN trial demonstrated that 1 g of tranexamic acid given to women with blood loss of more than 500 mL after vaginal delivery or 1000 mL after cesarean section has a risk reduction of death of 0.81 with no increased risk of thrombosis.⁷⁶ Given this abundant data, it is clear tranexamic acid needs to be part of any massive transfusion protocol.⁷⁷

RECOMBINANT FACTOR VIIa

Recombinant factor VIIa (rVIIa) was originally developed as a “bypass” agent to support hemostasis in hemophiliacs.⁷⁸ However, the use of rVIIa for a wide array of bleeding disorders, including patients with factor VII and XI deficiency and Glanzmann thrombasthenia, has been reported.⁷⁹ Increasingly, rVIIa is being used as a “universal hemostatic agent” for patients with uncontrolled bleeding from any mechanism.⁸⁰ Multiple case reports have described the use of rVIIa for bleeding in cardiac surgery patients, obstetrical bleeding, reversal of anticoagulation, and trauma.⁸¹ Unfortunately, little formal trial data exists to put these anecdotes into perspective, and formal review of clinical trial results has shown no benefit.^82,83 However, when used in older patients, especially those with vascular risk factors, the risk of arterial thrombosis appears to increase.⁸⁴ In the trials for intracranial hemorrhage, the thrombosis rate was 5% to 9%, and rates up to 10% for arterial events were seen in older patients in a review of all trials.^85–87 Given the lack of data but the evidence of risk, rVIIa use should be restricted to patients with documented bleeding disorders that have been shown to benefit by its use.